Tumor hypoxia is not a stable phenomenon but cycles between periods of deep hypoxia and reoxygenation. Cyclic hypoxia originates from heterogeneities in red blood cell flux and from the permanent remodelling of the angiogenic vascular network. Endothelial cells lining tumor blood vessels are therefore also influenced by cyclic hypoxia. The gene expression pattern promoted by cyclic hypoxia differs from those observed under normoxia and even continuous hypoxia. PTGS2 is one gene exquisitely up-regulated in endothelial cells (and tumor cells) in response to cyclic hypoxia. Elevated COX-2 (the PTGS2 gene product) expression and activity account for cyclic hypoxia-driven increase in endothelial cell survival and angiogenesis.
Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic hypoxia: effect on angiogenesis and metastases.
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View SamplesdMyc is a conserved transcription factor that controls growth and proliferation by regulating its target genes.
MicroRNA miR-308 regulates dMyc through a negative feedback loop in Drosophila.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
HIV‐exposed seronegative commercial sex workers show a quiescent phenotype in the CD4+ T cell compartment and reduced expression of HIV‐dependent host factors.
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View SamplesUnderstanding why some indidivual resist HIV-1 infection despite continued exposure is an important goal for vaccine development.
HIV‐exposed seronegative commercial sex workers show a quiescent phenotype in the CD4+ T cell compartment and reduced expression of HIV‐dependent host factors.
No sample metadata fields
View SamplesInvestigation of mRNA changes in podocytes transfected with a miR-93 mimic or a nontargeting mimic. Overall design: The design was meant to identify biologically significant, novel targets of the miR-93 microRNA in podocytes
miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy.
No sample metadata fields
View SamplesOur lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line spontaneously transformed into the spontaneously transformed OSE (STOSE) cell line in mid 2012.
A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.
Specimen part
View SamplesBackground: Type I interferons (IFNs) are essential to the clearance of viral diseases, in part by initiating upregulation of IFN regulated genes (IRGs). A clear distinction between genes upregulated directly by virus and genes upregulated by secondary IFN production has not been made. Here we investigated the genes regulated by IFN-a2b compared to the genes regulated by SARS-CoV infection in ferrets.
Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation.
Specimen part
View SamplesThe 2009 H1N1 influenza pandemic has prompted a significant need for the development of efficient, single-dose, adjuvanted vaccines. Here we investigated the adjuvant potential of CpG oligodeoxynucleotide (ODN) when used with a human seasonal influenza virus vaccine in ferrets. We found that the CpG ODNadjuvanted vaccine effectively increased antibody production and activated type I interferon (IFN) responses compared to vaccine alone. Based on these findings, pegylated IFN- 2b (PEG-IFN) was also evaluated as an adjuvant in comparison to CpG ODN and complete Freunds adjuvant (CFA). Our results showed that all three vaccines with adjuvant added prevented seasonal human A/Brisbane/59/2007 (H1N1) virus replication more effectively than did vaccine alone. Gene expression profiles indicated that, as well as upregulating IFN-stimulated genes (ISGs), CpG ODN enhanced B-cell activation and increased Toll-like receptor 4 (TLR4) and IFN regulatory factor 4 (IRF4) expression, whereas PEG-IFN augmented adaptive immunity by inducing major histocompatibility complex (MHC) transcription and Ras signaling. In contrast, the use of CFA as an adjuvant induced limited ISG expression but increased the transcription of MHC, cell adhesion molecules, and B-cell activation markers. Taken together, our results better characterize the specific molecular pathways leading to adjuvant activity in different adjuvant-mediated influenza virus vaccinations.
Molecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus.
Specimen part, Treatment
View SamplesN6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (“m6A levels”), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3’ untranslated regions (3’-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. Overall design: m6A-LAIC-seq of H1-ESC and GM12878 cell lines, each cell line has two replicates
m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome.
No sample metadata fields
View SamplesPurpose: Selecting muscle-invasive bladder cancer patients for adjuvant therapy is currently based on clinical variables with limited power. We hypothesized that genomic-based signatures can outperform clinical models to identify patients at higher risk. Method:Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set.
Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.
Specimen part
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